The Use of Ceramides to Predict Metabolic Response to Metformin in Women With PCOS

Anu Sharma; Benjamin Krick; Ying Li; Scott A Summers; Mary C Playdon; Corrine Welt

doi:10.1210/jendso/bvac131

The Use of Ceramides to Predict Metabolic Response to Metformin in Women With PCOS

J Endocr Soc. 2022 Sep 2;6(11):bvac131. doi: 10.1210/jendso/bvac131. eCollection 2022 Oct 11.

Authors

Anu Sharma¹, Benjamin Krick², Ying Li³, Scott A Summers^{3

4}, Mary C Playdon^{2

3

4}, Corrine Welt¹

Affiliations

¹ Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT, USA.
² Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
³ Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
⁴ Diabetes and Metabolism Research Center, University of Utah School of Medicine, Salt Lake City, UT, USA.

Abstract

Context: Polycystic ovarian syndrome (PCOS) is a complex disorder in which metabolic abnormalities are associated with reproductive dysfunction. Women with PCOS have increased ceramide concentrations. Previous studies demonstrated that treating metabolic abnormalities of PCOS with metformin improved glucose effectiveness after 12 weeks.

Objective: We evaluated whether, in women with PCOS, lower baseline ceramide, diacylglycerol (DAG), and triacylglycerol (TAG) concentrations were associated with improved metabolic response to metformin.

Methods: Women (n = 29), aged 29 ± 5 years and diagnosed with PCOS by the NIH criteria underwent an intravenous glucose tolerance test (IVGTT) before and after 12-week treatment with metformin (1500 mg per day). Metabolic responders were defined by improved glucose effectiveness, specifically, the ability of glucose to stimulate uptake and suppress production, after metformin treatment.

Results: Twelve weeks of metformin resulted in weight loss (-1.7 ± 2.6 kg, P < 0.01) and a reduction in BMI (-0.6 ± 0.9 kg/m², P < 0.01) with no change in HbA1c. The concentrations of Cer(d18:1/22:0), Cer(d18:1/24:0), total ceramides, total Cer(d16:0), total Cer(d18:2), DAG, dihydrosphingomyelin (DHSM), and TAG decreased after metformin treatment (P < 0.05). Baseline total Cer(d16:0) concentration <204.1 pmol/mL was 82% sensitive (AUC 0.72, P = 0.03) and total DHSM concentration <32237 pmol/mL was 100% specific (AUC 0.73, P = 0.03) in predicting improved metabolic response to metformin, as measured by IVGTT.

Conclusion: Lower total Cer(16:0) and DHSM concentrations are associated with a beneficial metabolic response to metformin in women with PCOS. Based on the known association between higher ceramide levels and type 2 diabetes, the data suggest that metformin improves metabolic parameters in women with mild metabolic derangements.

Keywords: ceramides; metformin; polycystic ovary syndrome; precision treatment.

Abstract

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